Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting

Malaria infection induces the production of serum antibodies to a variety of malaria antigens but the prevalence of antibodies to any particular antigen is typically much less than 100%, It has been assumed that non-responsiveness to defined antigens in malaria immune subjects is due to HLA-mediated restriction of the immune response. In this study we have investigated the role of HLA and non-HLA genes in the antibody response to two merozoite surface antigens (MSP1 and MSP2) and a sexual stage antigen (Pfs260/230) of Plasmodium falciparum, and conclude that host genotype is not a major determinant of responsiveness, Although antibody levels vary in accordance with seasonal variations in malaria transmission in semi-immune children, antibody levels remain stable in clinically immune adults, Antigen recognition is selective with individual donors showing consistent high titre responses to some antigens/epitopes whilst consistently failing to recognize adjacent regions/epitopes from the same protein, An alternative explanation, consistent with the data presented here, is that selective antibody responses to malaria antigens in immune individuals result from a process akin to clonal imprinting (original antigenic sin).